1. ¹Renal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
2. ²Endocrine Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
3. ³Pediatric Nephrology Unit, Departments of Medicine and Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

Correspondence: M Wolf, Renal Unit, Massachusetts General Hospital, Harvard Medical School, Bartlett 917, 55 Fruit Street, Boston, Massachusetts 02114, USA. E-mail: mswolf@partners.org

Received 23 February 2006; Revised 5 June 2006; Accepted 5 July 2006; Published online 30 August 2006.

Abstract

Hypophosphatemia is a common complication of kidney transplantation. Tertiary hyperparathyroidism has long been thought to be the etiology, but hypophosphatemia can occur despite low parathyroid hormone (PTH) levels and can persist after high PTH levels normalize. Furthermore, even in the setting of normal allograft function, hypophosphatemia, and hyperparathyroidism, calcitriol levels remain inappropriately low following transplantation, suggesting that mechanisms other than PTH contribute. Fibroblast growth factor-23 (FGF-23) induces phosphaturia, inhibits calcitriol synthesis, and accumulates in chronic kidney disease. We performed a prospective, longitudinal study of 27 living donor transplant recipients to test the hypotheses that excessive FGF-23 accounts for hypophosphatemia and decreased calcitriol levels following kidney transplantation. Hypophosphatemia <2.5 mg/dl developed in 85% of subjects, including one who had previously undergone parathyroidectomy; 37% developed phosphate 1.5 mg/dl. The mean pre-transplant FGF-23 level was 1,218542 RU/ml. Within the first week following transplantation, mean levels decreased to 557579 RU/ml, which were still above normal. FGF-23 was independently associated with serum phosphate (P<0.01), urinary excretion of phosphate (P<0.01), and calcitriol levels (P<0.01); PTH was not independently associated with any of these parameters. We calculated area under the curve for FGF-23 and PTH between the pre- and first post-transplant levels as a summary measure of early exposure to these phosphaturic hormones. An area under the FGF-23 curve greater than the median was associated with a relative risk of developing hypophosphatemia 1.5 mg/dl of 5.3 (P=0.02) compared with lower levels. Increased area under the PTH curve was not associated with greater risk of hypophosphatemia. Excessive FGF-23 exposure in the early post-transplant period appears to be more strongly associated with post-transplant hypophosphatemia than PTH.